Microencapsulation of Sulfadiazine with Cellulose Acetate Pethalate

Abstract

Microencapsulation of a relatively insoluble drug sulfadiazine was carried out by allowing drops of' a suspension of the drug in an aqueous cellulose acetate phthalate solution to fall into an acetic acid hardening solution. Spherical microcapsules could readily be obtained when a surfactant polyoxyethylene 20 sorbitan monooleate was added to the suspensior. Increased drug concentration in the suspension yielded larger microcapsules with shorter disintegration times. The incorporation of viscosity agents into the suspension yielded microcapsules with altered disintegration times     

Preparation and dissolution characteristics of indomethacin sustained release beads

Indomethacin is a nonsteroidal anti-inflammatory agent and has a short half life, and causes gastric irritation. Sustained release beads of indomethacin were prepared and dissolution profiles were investigated. Beads were prepared by allowing drops of a suspension of the drug and excipients in a solution of cellulose acetate phthalate to drop into an acetic acid solution by means of a peristaltic pump. In a previous study¹, sulfadiazine was used as a model drug to prepare beads by a similar method and the effects of various viscosity agents on the properties of these beads were assessed. Glycerin, polymers (Methocel and Avicel), and surfactants (Tween 80 and Span 80) were used as excipients. The incorporation of various viscosity agents and polymers into the suspension yielded beads with different disintegration and dissolution values. A high performance liquid chromatography method showed no indication of drug degradation during the preparation. The dissolution studies of the indomethacin preparations demonstrated differences in drug release properties depending on composition and method of preparation. The preparation with equal quantities of the two surfactants (Tween 80 and Span 80) released the drug at the slowest rate.     

Preparation and dissolution characteristics of indomethacin sustained release beads

Abstract

Indomethacin is a nonsteroidal anti-inflammatory agent and has a short half life, and causes gastric irritation. Sustained release beads of indomethacin were prepared and dissolution profiles were investigated. Beads were prepared by allowing drops of a suspension of the drug and excipients in a solution of cellulose acetate phthalate to drop into an acetic acid solution by means of a peristaltic pump. In a previous study¹, sulfadiazine was used as a model drug to prepare beads by a similar method and the effects of various viscosity agents on the properties of these beads were assessed. Glycerin, polymers (Methocel and Avicel), and surfactants (Tween 80 and Span 80) were used as excipients. The incorporation of various viscosity agents and polymers into the suspension yielded beads with different disintegration and dissolution values. A high performance liquid chromatography method showed no indication of drug degradation during the preparation. The dissolution studies of the indomethacin preparations demonstrated differences in drug release properties depending on composition and method of preparation. The preparation with equal quantities of the two surfactants (Tween 80 and Span 80) released the drug at the slowest rate.     

In Vitro/in Vivo Evaluation Of A Liquid Sustained Release Dosage Form Of Chlorpheniramine

Chlorpheniramine-resin complexes were coated with cellulose acetate butyrate to yield microcapsules with a geometric mean diameter of 346 μm. In vitro release rate of chlorpheniramine declined with increasing microcapsule size. Release of chlorpheniramine from the micropcapsules was faster in simulated gastric fluid (pH 1.2) than in simulated intestinal fluid (pH 7.5). A Chlorpheniramine solution administered by rapid intravenous injection to dogs exhibited a two phase decline in plasma drug concentration. A peroral solution resulted in a rapid rise to a peak followed by a sharp decline in plasma chlorpheniramine concentration. Peroral administration of a microcapsule suspension caused a rapid rise in plasma concentration, but prevented the fast decline.     

Formulation factors affecting drug release from poly(lactic acid) (PLA) microcapsule tablets

A sustained-release (SR) formulation of phenobarbital (PB) microcapsule tablet was prepared using low molecular weight (MW) DL- and high MW L-poly(lactic acid) (PLA) polymer. Microencapsulation of PB showed a unimodal size distribution (375 to 550 microns) of the microcapsules with high loading capacity (> 84%). Drug release from the microcapsule was influenced by the polymer ratios and increased with an increase in L-PLA amount. Microcapsules and physical mixtures of PB and the PLA were directly compressed independently to form microcapsule and matrix tablets, respectively. Drug release from the microcapsule tablets was significantly lowered (p < .001) compared to matrix tablets or free microcapsule (free microcapsule > matrices > microcapsule tablets). We also investigated the effect of tablet adjuvants, compression pressures, and microcapsule loading on the tablet performance in terms of friability, hardness, porosity, tensile strength, and the release kinetics of PB. The drug release rate increased with increasing compression pressure in the case of Emcompress or lactose, but not Avicel. The drug release rate was three- to fivefold increased with sodium starch glycolate compared to tablets without a disintegrant. With an increase in microcapsule loading, a decrease in the drug release rate was observed; however, the tablet performance remained satisfactory. The morphology of the microcapsules was monitored microscopically after the dissolution and the disintegration of tablets. The drug release accelerated with compression pressures and microcapsule loading from the tablets due to mechanical destruction of the microcapsule wall, which was more clearly seen after disintegration and dissolution of the tablets. Our data suggest that the PLA microcapsule can be tableted to make a SR product without significantly affecting its release kinetics.     

Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N₂ adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 μm, and had a specific surface area of about 306 m²/g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties.     

Preparation and Characterization of Ethylcellulose-Walled Theophylline Microcapsules Using the Emulsion-Solvent Evaporation Technique

Ethylcellulose microcapsules containing theophylline are prepared by emulsification of a organic ethylcellulose solution in a oil phase containing a surfactant. The preparation is based on dispersion of acetone containing the drug in liquid paraffin. Tween 80 was used as a dispersing agent. Good reproducibility in microcapsule preparation was observed. The microcapsules obtained were uniform and free-flowing particles. The type of the stirring-manner (propella - and magnet - stirring), and the drug to polymer ratios have an important influence on the in vitro dissolution and release of theophylline from microcapsules.     

In Vitro/in Vivo Evaluation Of A Liquid Sustained Release Dosage Form Of Chlorpheniramine

Abstract

Chlorpheniramine-resin complexes were coated with cellulose acetate butyrate to yield microcapsules with a geometric mean diameter of 346 μm. In vitro release rate of chlorpheniramine declined with increasing microcapsule size. Release of chlorpheniramine from the micropcapsules was faster in simulated gastric fluid (pH 1.2) than in simulated intestinal fluid (pH 7.5). A Chlorpheniramine solution administered by rapid intravenous injection to dogs exhibited a two phase decline in plasma drug concentration. A peroral solution resulted in a rapid rise to a peak followed by a sharp decline in plasma chlorpheniramine concentration. Peroral administration of a microcapsule suspension caused a rapid rise in plasma concentration, but prevented the fast decline.     

Electric-Field-Controlled Adsorption of Microcapsules under Fabrication of Planar Structures

It is found that an electric field applied parallel to a substrate surface influences the adsorption of positively charged core–shell microcapsules on glass substrates. As a result, the amount of microcapsules adsorbed near negative contact is up to 2 times larger than the one absorbed near positive contact. It is also found that small concentration (less than 0.2 M) of salt in microcapsule suspension decreases this effect, while an increase in the concentration to 0.45 M results in enhancement of the effect.     

The Effect of Indomethacim Microcapsules on Intestinal Ulceration in the Rat

The absorption of indomethacin in the rat was studied following a single oral dose of indomethacin in the form of the powdered drug or microcapsules.

Serum levels of unmetabolized drug were measured and gastrointestinal ulceration was assessed 72 hours after dosing by measuring the tensile strength of the intestine after its removal from the animal and by counting the number of ulcers present on the intestinal wall.

In vitro dissolution of the powdered drug and microcapsules was carried out in water, in Polyethylene Glycol solution and in 40mM sodium cholate solution for a comparison with the in vivo results.

Both in vitro and in vivo results for the microcapsules were similar to those of the powdered drug and therefore encapsulation of indomethacin offered no advantage over conventional dosage forms.     

A Study of the Effects of Sucrose Concentration,Lacquer Concentration and Coating Time on the Formulation of Stable and Effective Carbenicillin Indanyl Sodium Microcapsules

Abstract

Carbenicillin indanyl sodium, commonly known as Geocillin (GC), is an orally effective derivative of carbenicillin employed in the treatment of gram negative infections of the urinary tract. GC exhibits an extremely bitter taste which affects patient compliance upon oral dosing (1). A novel coating approach allows Geocillin to be prepared as a suspension for oral administration. GC is available only as a tablet.

Eudragit E100^R [EE] is a tasteless, acid soluble cationic polymer. Encapsulation of GC with [EE] inhibited its release in the mouth, thus overcoming its bitter taste. Dissolution studies were carried out in simulated gastric fluid and simulated intestinal fluid. Three factors, viz. sucrose concentration, lacquer concentration and coating time were evaluated to arrive at an optimally acceptable formulation.

The formulation containing GC and sucrose in the ratio of 1:3, suspension coated using a 5% w/w lacquer solution for 40 mins. yielded taste free microcapsules with optimal release characteristics.     

The Effect of Indomethacim Microcapsules on Intestinal Ulceration in the Rat

Abstract

The absorption of indomethacin in the rat was studied following a single oral dose of indomethacin in the form of the powdered drug or microcapsules.

Serum levels of unmetabolized drug were measured and gastrointestinal ulceration was assessed 72 hours after dosing by measuring the tensile strength of the intestine after its removal from the animal and by counting the number of ulcers present on the intestinal wall.

In vitro dissolution of the powdered drug and microcapsules was carried out in water, in Polyethylene Glycol solution and in 40mM sodium cholate solution for a comparison with the in vivo results.

Both in vitro and in vivo results for the microcapsules were similar to those of the powdered drug and therefore encapsulation of indomethacin offered no advantage over conventional dosage forms.     

Evaluation of Spray-Drying as a Method to Prepare Microparticles for Controlled Drug Release

The possibility to obtain microcapsules or microspheres for controlled release by spray-drying is evaluated. Drugs of different solubilities like theophylline and sodium sulfamethazine, with Eudragit RS as coating polymer, are chosen.

The polymer is used, either dissolved in an hydroalcoholic solution or suspended (pseudolatex) in water, in different weight ratios with the drug. The obtained solution or suspension is spray-dried.

Scanning electron microscope analysis of the powders reveals no sign of microencapsulation. Moreover, only a fraction of the particles has a spherical shape.

For each spray-dried powder, a part of the obtained particles is compressed into tablets, and the rest is stored.

Dissolution studies in distilled water at 37 C are performed on powders and tablets.

While the uncompressed microparticles do not give any controlled release, the tablets show an ability in slowing down drug delivery greater than the one obtained with the traditional methods.     

Evaluation of Spray-Drying as a Method to Prepare Microparticles for Controlled Drug Release

The possibility to obtain microcapsules or microspheres for controlled release by spray-drying is evaluated. Drugs of different solubilities like theophylline and sodium sulfamethazine, with Eudragit RS as coating polymer, are chosen.

The polymer is used, either dissolved in an hydroalcoholic solution or suspended (pseudolatex) in water, in different weight ratios with the drug. The obtained solution or suspension is spray-dried.

Scanning electron microscope analysis of the powders reveals no sign of microencapsulation. Moreover, only a fraction of the particles has a spherical shape.

For each spray-dried powder, a part of the obtained particles is compressed into tablets, and the rest is stored.

Dissolution studies in distilled water at 37 C are performed on powders and tablets.

While the uncompressed microparticles do not give any controlled release, the tablets show an ability in slowing down drug delivery greater than the one obtained with the traditional methods.     

Development of biodegradable microcapsules as carrier for oral controlled delivery of amifostine

The primary objective of this project was to develop a biodegradable, orally active controlled-release formulation of amifostine. Development of such a formulation will mark an important advancement in the areas of chemoprotection and radioprotection. Biodegradable microcapsules of amifostine were prepared using poly(lactide/glycolide) (PLGA 50:50). The microcapsules were prepared by solvent evaporation technique. Amifostine-loaded microcapsules were evaluated for particle size, surface morphology, thermal characteristics, and drug release. Particle size and surface morphology were determined using scanning electron microscopy (SEM). Thermal characterization was conducted using differential scanning calorimetry (DSC). In vitro release study was performed at 37°C using phosphate buffer (pH 7.4). Amifostine release was calculated by measuring the amount of drug remaining within the microcapsules at a specific sampling time. The amount of amifostine in the samples was determined by high-performance liquid chromatography (HPLC) using an electrochemical detector. The yield of microcapsules was 75%. Scanning electron microscopy pictures revealed that the particles were nearly spherical and smooth with an average size of 54 µm. Differential scanning calorimetry thermograms showed that microcapsules loaded with amifostine have a glass transition at 39.4°C, and the melting endotherm of amifostine was absent. The absence of a melting endotherm for amifostine was an indication that amifostine was not in the crystalline state in the microcapsules, but rather in the form of a solid solution in PLGA. Approximately 50% amifostine was released during the first 6 hr of the in vitro release study. The drug, however, continued to release over the observed period of 12 hr during which 92% amifostine was released.     

Characteristics and release property of polylactic acid/sodium monofluorophosphate microcapsules prepared by spray drying

Microcapsules composed of polylactic acid (PLA)/corrosion inhibitor sodium monofluorophosphate (MFP) were prepared by spray drying, and the effects of processing parameters on the morphology and encapsulation efficiency of the microcapsules were investigated. The results showed that low viscous PLA solution only resulted in porous microcapsules with low encapsulation efficiency, whereas filamentous substances were produced instead of microcapsules once PLA solution content exceeded 5%. When spray pressure exceeded 0.4 MPa, the microcapsule surface was wrinkled due to high evaporation rate of the atomized droplets. The spray pressure less than 0.3 MPa created larger atomized droplets and yielded the adhesive microcapsules with lower encapsulation efficiency. The optimal emulsion parameters were as follows: PLA concentration, 5%; water-oil ratio, 1:9; inlet air temperature, 50 °C; and spray pressure, 0.4 MPa. The resulting microcapsules exhibited a good sustained-release behavior in a simulated concrete pore solution.     

聚氨基酸复合微胶囊对Hb的控制释放

以生物相容性好、价格低廉的海藻酸钠(ALG)为聚阴离子芯材,通过静电液滴装置制备了平均粒径在290 μm左右、球形度好、表面光洁的海藻酸钙胶珠;再将生物可降解、具有介入治疗作用的聚精氨酸(PLA)与聚组氨酸(PLH)的混合物作为聚阳离子壁材,在海藻酸钙胶珠表面覆上一层高分子聚合膜以制备聚氨基酸复合微胶囊;并以牛血红蛋白Hb为药物模型,对微胶囊的控制释放性能进行了考察并将其初步应用于体外模拟口服给药。结果表明:聚氨基酸复合微胶囊在前0.5 h的累积释放量均低于40％,溶出结束时累积释放量均达到80%以上;ALG/(PLA-PLH)复合微胶囊和ALG/PLH微胶囊的药物释放速率均低于ALG/PLA微胶囊;于10 min成膜时间内制备的微胶囊具有较高的载药量、包封率和缓释性能;以pH 4.6 HAc-NaAc缓冲液为成膜溶媒制备的微胶囊,Hb持续释放时间和残留量均高于蒸馏水组;前2 h在模拟胃液的pH 1.2 HCl溶媒中累计释放的Hb不超过10％且绝大部分是在模拟肠液环境即pH 6.8 PBS 溶媒中释放的;壳聚糖的引入能在一定程度上延长药物释放时间。聚氨基酸复合微胶囊具备一定的缓释性、pH响应性和生理黏附性,有望成为一种口服给药系统用药物载体。      

Stability investigation of FCC-based tablets for oral suspension with caffeine and oxantel pamoate as model drugs

Tablets for oral suspension (TOS) present a convenient alternative dosage form to conventional tablets. Dispersed in a glass of water or on a spoon, such tablets can be easily administered, which can become beneficial for pediatric or geriatric patients. The novel excipient functionalized calcium carbonate (FCC), consisting of calcium carbonate and calcium phosphate, has already shown to be suitable to produce orally disintegrating placebo tablets. In this study, the influence of formulation composition on disintegration time in water and artificial saliva was investigated using caffeine and oxantel pamoate as model drugs, reflecting BCS class 1 and BCS class 4, respectively. The optimized formulation for each model drug underwent a stress test. The results show that the drug content in DTs was not influenced by FCC under stressed conditions, however the disintegration and dissolution performance was affected by temperature and humidity. It can be concluded that it was possible to produce TOS characterized by rapid disintegration complemented by high physical stability of the tablets and chemical stability of the drug.     

Drug Release Properties of the Microcapsules of Adriamycin Hydrochloride with Ethylcellulose Prepared by a Phase Separation Technique

Adriamycin hydrochloride was microencapsulated with ethylcellulose by a phase separation method to develop a prolonged release dosage form. Polyisobutylene (PIB) was used as a coacervation-inducing agent to control the particle size and drug release rate of the resultant microcapsules. With increasing the concentration of PIB (1 to 3 %) the average diameter of the microcapsules decreased, due to the fact that the microcapsules were discreted to a single microcapsule. At low concentration of PIB, the resultant microcapsules were agglomerated, which resulted in increasing the size. The microcapsules prepared with PIB 2 % prolonged desirably the drug release from the microcapsules. A little size effects of the microcapsules on the drug release rate was found for the microcapsules with PIB 2 % and 3 %.     

A Study on the Manufacture and in Vitro Dissolution of Terbutaline Sulfate Microcapsules and their Tablets

Microcapsules of terbutaline sulfate with cellulose acetate butyrate and ethylcellulose were prepared using an emulsion-solvent evaporation technique. The in vitro dissolution of terbutaline sulfate was studied using the USP rotating basket method. As the polymer to drug ratio increased, the microcapsule size distribution shifted to the smaller size and the release of terbutaline sulfate decreased. The release of terbutaline sulfate was independent of the dissolution medium pH for both polymers. The release kinetics from the microcapsules was dependent on the polymer type and polymer to drug ratio. The release of terbutaline sulfate from cellulose acetate butyrate and ethylcellulose microcapsules formulated with a 1:1 polymer to drug ratio was complex and could not be differentiated between the square-root of time and first-order release models. However, the square-root of time model was followed by microcapsules formulated with a 2:1 or a 3:1 cellulose acetate butyrate to drug ratio. When the ethylcellulose to drug ratio was increased to 2:1 the square-root of time model was followed. At an ethylcellulose to drug ratio of 3:1 the release kinetics could not be differentiated between the Hixon-Crowell and first-order release models. The T50% from ethylcellulose microcapsules was decreased when the microcapsules were compressed into tablets with the addition of Avicel^R/Emcompress^R (2:1) or Avicel^R.